The objective of this project is to detect natural and induced mutations in mice for the purpose of providing understanding of the specific molecular events involved in germinal mutation and the effects of these events on the life, form and function of the mammalian organism. Results are relevant to human exposures to mutagens and the potential for increased risk of genetic disease that may accompany mutagen exposure. The problem is approached by detecting mutations at specific biochemical loci with electrophoretic methods, by conducting characterization studies on the mutant genes and gene product, and by examining the animals for expressed physical abnormalities correlated with mutation rate increases and with specific induced-mutant genotypes. The methods have led to successful identification of many new mutations induced by ethylnitrosourea, x-rays and ethylene oxide. A number of naturally occurring mutations have been identified as well. Results have generally shown little or no increased incidence of harmful gene expression attributable to induced mutations. The results raise questions as to the appropriateness of depending on the mutagenic properties of a substance for environmental risk assessment.